GATA1

GATA1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases GATA1, ERYF1, GATA-1, GF-1, GF1, NF-E1, NFE1, XLANP, XLTDA, XLTT, GATA binding protein 1
External IDs OMIM: 305371 MGI: 95661 HomoloGene: 1549 GeneCards: GATA1
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

2623

14460

Ensembl

ENSG00000102145

ENSMUSG00000031162

UniProt

P15976

P17679

RefSeq (mRNA)

NM_002049

NM_008089

RefSeq (protein)

NP_002040.1

NP_032115.1

Location (UCSC) Chr X: 48.79 – 48.79 Mb Chr X: 7.96 – 7.98 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Erythroid transcription factor also known as GATA-binding factor 1 or GATA-1 is a protein that in humans is encoded by the GATA1 gene.[3]

GATA-1 is a member of the GATA transcription factor family and is a key mediator of the development of specific types of blood cells from their precursor cells, termed hematopoietic progenitors or precursors.[4][5] This protein plays a role in erythroid development by regulating a large ensemble of genes that mediate both the development and function of red blood cells. Critical functions in the developing red blood cell (erythroblast) include the establishment of the erythroid cytoskeleton, enzymes that mediate heme biosynthesis, and polypeptide chains that constitute the hemoglobin tetramer. Mutations in the gene encoding GATA-1 have been associated with X-linked dyserythropoietic anemia and thrombocytopenia.[6]

Function

GATA1 is required for the maturation of red blood cells, megakaryocytes, mast cells and eosinophils.[7] GATA1 mutant mice die in early embryonic development due to inability to form mature erythroid cells. GATA1 mutation in humans causes congenital anemias and thrombocytopenias.[8][9]

GATA1 was first described as a red blood cell lineage transcription factor that activates the beta-globin gene.[10] During red blood cell maturation, GATA1 activates nearly all erythroid-specific genes while silencing genes associated with the immature proliferative red blood cell precursor cells (erythroblasts).[11][12] Genome-wide studies have provided evidence that GATA1 activates and represses a large number of genes.[11][12][13][14] Many questions remain unanswered regarding the function of a large number of genes. By contrast, other GATA-1 target genes have established activities to control fundamental cell biological functions, including machinery that controls the ability of erythroid precursor cells to proliferate and proteins that control the capacity of the erythroid precursor cell to remodel its organelles such as mitochondria,[15] proteins that control the RNA content of the erythroid precursor cell,[16] and proteins that control signal transduction networks that orchestrate the many dynamic transitions of the developing erythroid precursor.[17]

Structure

The GATA-1 protein contains multiple functional domains including the C-finger, the N-finger, and N-terminal sequences that have been suggested to constitute a transcriptional activation domain. The C-finger, named for being near the C-terminal, mediates Zinc finger sequence-specific DNA binding. The primary function of the N-finger, named for being near the N-terminal is binding to a cofactor named FOG1 (friend of GATA), although it has also been implicated in binding to naked DNA (DNA studied in the test tube that is not assembled into chromatin). The gene for GATA1 is on the X-chromosome.

Disease linkage

Mutations in GATA1 cause anemias and thrombocytopenia in human patients.[18][19] Disease-causing GATA1 mutations are present in the zinc finger DNA binding domains as well as protein-protein interaction domains of GATA1.[20]

Mutations in exon 2 of the GATA1 gene are present in almost all cases of Down syndrome (DS)-associated acute megakaryoblastic leukemia (AMKL).[21][22] While AMKL is typically associated with the (1;22) translocation and expression of a mutant fusion protein, the genetic alterations that promote individuals with DS-AMKL are related to the GATA1 mutations, and the formation of a truncated transcription factor (GATA1s).

The same mutations in exon 2 of GATA1 present in almost all Down Syndrome-associated transient myeloproliferative disorder (TMD) or transient leukemia (TL), a precursor condition that evolves into AMKL in 30% of patients, that as many as 10% of Down Syndrome children may develop.[23] The incidence for the GATA1 mutation in about 4% of Down Syndrome patients, but less than 10% of those with the mutation developed AMKL.[24] This mutation is present in the fetus, suggesting an early role in leukemogenesis. In addition to screening for TL, a GATA1 mutation at birth might serve as a bio-marker for an increased risk of DS-related AMKL.[25]

Interactions

GATA1 has been shown to interact with several proteins - either directly by binding the protein or indirectly (functional interaction without direct binding).

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ Caiulo A, Nicolis S, Bianchi P, Zuffardi O, Bardoni B, Maraschio P, Ottolenghi S, Camerino G, Giglioni B (Feb 1991). "Mapping the gene encoding the human erythroid transcriptional factor NFE1-GF1 to Xp11.23". Human Genetics. 86 (4): 388–90. doi:10.1007/bf00201840. PMID 1999341.
  4. ↑ Bresnick EH, Katsumura KR, Lee HY, Johnson KD, Perkins AS (2012). "Master regulatory GATA transcription factors: mechanistic principles and emerging links to hematologic malignancies". Nucleic Acids Res. 40 (13): 5819–31. doi:10.1093/nar/gks281. PMC 3401466Freely accessible. PMID 22492510.
  5. ↑ Bresnick EH, Lee HY, Fujiwara T, Johnson KD, Keles S (2010). "GATA switches as developmental drivers". J. Biol. Chem. 285 (41): 31087–93. doi:10.1074/jbc.R110.159079. PMC 2951181Freely accessible. PMID 20670937.
  6. ↑ "Entrez Gene: GATA1 GATA binding protein 1 (globin transcription factor 1)".
  7. ↑ Crispino JD (Feb 2005). "GATA1 in normal and malignant hematopoiesis". Seminars in Cell & Developmental Biology. 16 (1): 137–47. doi:10.1016/j.semcdb.2004.11.002. PMID 15659348.
  8. ↑ Fujiwara Y, Browne CP, Cunniff K, Goff SC, Orkin SH (Oct 1996). "Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1". Proceedings of the National Academy of Sciences of the United States of America. 93 (22): 12355–8. doi:10.1073/pnas.93.22.12355. PMC 37995Freely accessible. PMID 8901585.
  9. ↑ Campbell AE, Wilkinson-White L, Mackay JP, Matthews JM, Blobel GA (Jun 2013). "Analysis of disease-causing GATA1 mutations in murine gene complementation systems". Blood. 121 (26): 5218–27. doi:10.1182/blood-2013-03-488080. PMC 3695365Freely accessible. PMID 23704091.
  10. ↑ Evans T, Reitman M, Felsenfeld G (Aug 1988). "An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes". Proceedings of the National Academy of Sciences of the United States of America. 85 (16): 5976–80. doi:10.1073/pnas.85.16.5976. PMC 281888Freely accessible. PMID 3413070.
  11. 1 2 Welch JJ, Watts JA, Vakoc CR, Yao Y, Wang H, Hardison RC, Blobel GA, Chodosh LA, Weiss MJ (Nov 2004). "Global regulation of erythroid gene expression by transcription factor GATA-1". Blood. 104 (10): 3136–47. doi:10.1182/blood-2004-04-1603. PMID 15297311.
  12. 1 2 Cheng Y, Wu W, Kumar SA, Yu D, Deng W, Tripic T, King DC, Chen KB, Zhang Y, Drautz D, Giardine B, Schuster SC, Miller W, Chiaromonte F, Zhang Y, Blobel GA, Weiss MJ, Hardison RC (Dec 2009). "Erythroid GATA1 function revealed by genome-wide analysis of transcription factor occupancy, histone modifications, and mRNA expression". Genome Research. 19 (12): 2172–84. doi:10.1101/gr.098921.109. PMC 2792182Freely accessible. PMID 19887574.
  13. ↑ Yu M, Riva L, Xie H, Schindler Y, Moran TB, Cheng Y, Yu D, Hardison R, Weiss MJ, Orkin SH, Bernstein BE, Fraenkel E, Cantor AB (Nov 2009). "Insights into GATA-1-mediated gene activation versus repression via genome-wide chromatin occupancy analysis". Molecular Cell. 36 (4): 682–95. doi:10.1016/j.molcel.2009.11.002. PMC 2800995Freely accessible. PMID 19941827.
  14. ↑ Fujiwara T, O'Geen H, Keles S, Blahnik K, Linnemann AK, Kang YA, Choi K, Farnham PJ, Bresnick EH (2009). "Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy". Mol. Cell. 36 (4): 667–81. doi:10.1016/j.molcel.2009.11.001. PMC 2784893Freely accessible. PMID 19941826.
  15. ↑ Kang YA, Sanalkumar R, O'Geen H, Linnemann AK, Chang CJ, Bouhassira EE, Farnham PJ, Keles S, Bresnick EH (2012). "Autophagy driven by a master regulator of hematopoiesis". Mol. Cell. Biol. 32 (1): 226–39. doi:10.1128/MCB.06166-11. PMC 3255705Freely accessible. PMID 22025678.
  16. ↑ McIver SC, Kang YA, DeVilbiss AW, O'Driscoll CA, Ouellette JN, Pope NJ, Camprecios G, Chang CJ, Yang D, Bouhassira EE, Ghaffari S, Bresnick EH (2014). "The exosome complex establishes a barricade to erythroid maturation". Blood. 124 (14): 2285–97. doi:10.1182/blood-2014-04-571083. PMID 25115889.
  17. ↑ Hewitt KJ, Kim DH, Devadas P, Prathibha R, Zuo C, Sanalkumar R, Johnson KD, Kang YA, Kim JS, Dewey CN, Keles S, Bresnick EH (2015). "Hematopoietic Signaling Mechanism Revealed from a Stem/Progenitor Cell Cistrome". Mol. Cell. 59 (1): 62–74. doi:10.1016/j.molcel.2015.05.020. PMID 26073540.
  18. ↑ Crispino JD, Weiss MJ (May 2014). "Erythro-megakaryocytic transcription factors associated with hereditary anemia". Blood. 123 (20): 3080–8. doi:10.1182/blood-2014-01-453167. PMC 4023417Freely accessible. PMID 24652993.
  19. ↑ Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM, Weiss MJ (Mar 2000). "Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1". Nature Genetics. 24 (3): 266–70. doi:10.1038/73480. PMID 10700180.
  20. ↑ Campbell AE, Wilkinson-White L, Mackay JP, Matthews JM, Blobel GA (Jun 2013). "Analysis of disease-causing GATA1 mutations in murine gene complementation systems". Blood. 121 (26): 5218–27. doi:10.1182/blood-2013-03-488080. PMC 3695365Freely accessible. PMID 23704091.
  21. ↑ Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM, Crispino JD (Sep 2002). "Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome". Nature Genetics. 32 (1): 148–52. doi:10.1038/ng955. PMID 12172547.
  22. ↑ Rainis L, Bercovich D, Strehl S, Teigler-Schlegel A, Stark B, Trka J, Amariglio N, Biondi A, Muler I, Rechavi G, Kempski H, Haas OA, Izraeli S (Aug 2003). "Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21". Blood. 102 (3): 981–6. doi:10.1182/blood-2002-11-3599. PMID 12649131.
  23. ↑ Greene ME, Mundschau G, Wechsler J, McDevitt M, Gamis A, Karp J, Gurbuxani S, Arceci R, Crispino JD (2003). "Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome". Blood Cells, Molecules & Diseases. 31 (3): 351–6. doi:10.1016/j.bcmd.2003.08.001. PMID 14636651.
  24. ↑ Pine SR, Guo Q, Yin C, Jayabose S, Druschel CM, Sandoval C (Sep 2007). "Incidence and clinical implications of GATA1 mutations in newborns with Down syndrome". Blood. 110 (6): 2128–31. doi:10.1182/blood-2007-01-069542. PMID 17576817.
  25. ↑ Shimada A, Xu G, Toki T, Kimura H, Hayashi Y, Ito E (Jan 2004). "Fetal origin of the GATA1 mutation in identical twins with transient myeloproliferative disorder and acute megakaryoblastic leukemia accompanying Down syndrome". Blood. 103 (1): 366. doi:10.1182/blood-2003-09-3219. PMID 14684662.
  26. 1 2 Lamonica JM, Deng W, Kadauke S, Campbell AE, Gamsjaeger R, Wang H, Cheng Y, Billin AN, Hardison RC, Mackay JP, Blobel GA (May 2011). "Bromodomain protein Brd3 associates with acetylated GATA1 to promote its chromatin occupancy at erythroid target genes". Proceedings of the National Academy of Sciences of the United States of America. 108 (22): E159–68. doi:10.1073/pnas.1102140108. PMC 3107332Freely accessible. PMID 21536911.
  27. ↑ Gamsjaeger R, Webb SR, Lamonica JM, Billin A, Blobel GA, Mackay JP (Jul 2011). "Structural basis and specificity of acetylated transcription factor GATA1 recognition by BET family bromodomain protein Brd3". Molecular and Cellular Biology. 31 (13): 2632–40. doi:10.1128/MCB.05413-11. PMID 21555453.
  28. ↑ Stonestrom AJ, Hsu SC, Jahn KS, Huang P, Keller CA, Giardine BM, Kadauke S, Campbell AE, Evans P, Hardison RC, Blobel GA (Feb 2015). "Functions of BET proteins in erythroid gene expression". Blood. 125: 2825–34. doi:10.1182/blood-2014-10-607309. PMID 25696920.
  29. ↑ Lahiri K, Dole MG, Vidwans AS, Kamat J, Kandoth P (Apr 1989). "Acute glomerulonephritis". Journal of Tropical Pediatrics. 35 (2): 92. doi:10.1093/tropej/35.2.92. PMID 2724402.
  30. ↑ Starck J, Cohet N, Gonnet C, Sarrazin S, Doubeikovskaia Z, Doubeikovski A, Verger A, Duterque-Coquillaud M, Morle F (Feb 2003). "Functional cross-antagonism between transcription factors FLI-1 and EKLF". Molecular and Cellular Biology. 23 (4): 1390–402. doi:10.1128/MCB.23.4.1390-1402.2003. PMC 141137Freely accessible. PMID 12556498.
  31. ↑ Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, Naoe T, Saito H (Dec 2003). "Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation". Oncogene. 22 (57): 9176–84. doi:10.1038/sj.onc.1206902. PMID 14668799.
  32. ↑ Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH (Oct 1995). "Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1". Proceedings of the National Academy of Sciences of the United States of America. 92 (21): 9585–9. doi:10.1073/pnas.92.21.9585. PMC 40846Freely accessible. PMID 7568177.
  33. ↑ Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, Dumenil D, Strouboulis J, Romeo PH, Hoang T (Jan 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". The EMBO Journal. 25 (2): 357–66. doi:10.1038/sj.emboj.7600934. PMC 1383517Freely accessible. PMID 16407974.
  34. ↑ Labbaye C, Quaranta MT, Pagliuca A, Militi S, Licht JD, Testa U, Peschle C (Sep 2002). "PLZF induces megakaryocytic development, activates Tpo receptor expression and interacts with GATA1 protein". Oncogene. 21 (43): 6669–79. doi:10.1038/sj.onc.1205884. PMID 12242665.
  35. ↑ Holmes M, Turner J, Fox A, Chisholm O, Crossley M, Chong B (Aug 1999). "hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation". The Journal of Biological Chemistry. 274 (33): 23491–8. doi:10.1074/jbc.274.33.23491. PMID 10438528.

Further reading

External links

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